In order to supply nutrients vital for sustaining life, such as carbohydrates, amino acids, and electrolytes, to a patient who cannot be supplied with nutrients orally or is insufficiently supplied with nutrients orally, intravenous nutrition therapy in which an infusion is administered through a vein is widely performed. The intravenous nutrition therapy is roughly classified into central venous nutrition therapy and peripheral venous nutrition therapy, by the route of administration.
In the central venous nutrition therapy, an infusion high in calories is administered through the central vein for a relatively long time. Accordingly, it is necessary to appropriately add vitamins and trace elements that could become deficient during the period of administration. In clinical practice, vitamin formulations and trace element formulations are added at the time of use by being mixed in the infusion. However, the mixing operation is cumbersome, and there is a concern that bacterial contamination or ingress of foreign substances will be caused by the mixing operation, which may be a cause of medical malpractice. Therefore, regarding a high-calorie infusion for administration through a central vein that is used for a long time, a formulation which contains reducing sugar, amino acids, electrolytes, and vitamins and in which solutions can be mixed in a sterile state is under development and has been commercialized. For example, PTLs 1 and 2 and NPLs 1 and 2 disclose an infusion formulation for central venous nutrition that is mixed with vitamins.
On the other hand, in the peripheral venous nutrition therapy, a nutrition infusion containing about 30% to 60% of the calories administered by the central venous nutrition therapy is administered through the peripheral vein. Duration of administration thereof is relatively short, such as 3 days to 2 weeks, and initially, mixing of vitamins was not particularly considered for the peripheral venous nutrition therapy. However, it is reported that the vitamin B1 concentration is reduced during the peripheral venous nutrition therapy (NPL 3). Vitamin B1 deficiency is highly likely to cause serious side-effects such as lactic acidosis, and accordingly, in order to improve safety, a nutrition infusion formulation for peripheral vein administration mixed with vitamin B1 in advance is reported (PTL 3). In addition, several formulations have been commercialized (NPLs 4, 5, and 6).
In recent years, it has been a reported that deficiency of vitamins other than vitamin B1 can be potentially caused in patients receiving infusion through a peripheral vein, and that it should be considered that the infusion for a peripheral vein should also be mixed with plural vitamins that are particularly necessary for the metabolism of sugar and amino acids (PTL 4).
However, each of the components including reducing sugar, amino acids, electrolytes, and vitamins shows sufficient stability or solubility in different pH regions. On the other hand, regarding the nutrition infusion for administration through a peripheral vein, if the pH of infusion is acidic at the time of administration, phlebitis or angialgia is easily caused, so it is desired that the pH be neutral. In addition, some of the respective components interact with each other. Therefore, in consideration of this point, a stable nutrition infusion for administration through a peripheral vein mixed in advance with vitamins is desired.
For example, folic acid causes turbidity in the acidic region of a sugar electrolyte solution, and even when mixed with an amino acid solution, folic acid causes incompatibility if vitamin B2, vitamin C, and the like coexist, so it is difficult to obtain a stable formulation. Therefore, for the infusion for administration through a central vein mixed with vitamins, which is used for the central venous nutrition therapy, a third chamber separated from the sugar electrolyte or amino acid solution is provided to separate the folic acid from the sugar electrolyte solution or vitamins B2 and C, so as to stabilize the infusion (PTL 2, NPLs 1 and 2). In addition, there is a disclosure regarding a method of mixing vitamins with an infusion for administration through a central vein that includes two solutions of a sugar solution and an amino acid solution. However, in this infusion, pH of the sugar solution and amino acid solution is 3.5 to 4.5 and 5.0 to 7.0, respectively, so the pH of the both solutions is acidic (PTLs 5 and 6). Moreover, regarding a nutrition infusion for administration through a peripheral vein, PTL 4 discloses an infusion for administration through a peripheral vein that is mixed with a vitamin B group, which is obtained by mixing vitamin B12 in an amino acid solution not containing sulfite, and mixing vitamin B1 in a sugar solution. However, PTL 4 discloses that since vitamin C, biotin, pantothenic acid, and the like sometimes decompose other vitamin B groups, it is preferable to add those components immediately before the administration.